Project Summary Major depression is quite prevalent: recent data suggest that approximately 7 percent of U.S. residents have experienced major depression in the previous year. The goal of depression treatment is to help individuals achieve symptomatic remission and normal social and role functioning. Even when patients do have some response to treatment, they often do not reach that goal. A partial response to treatment is associated with increased risk for relapse, for suicide, and for poorer psychosocial functioning relative to those who fully respond to treatment. When individuals have a partial response to antidepressant treatments, a key treatment option is augmentation. Traditionally, another medication or psychotherapy would be used to augment the initial medication. However, patients may have concerns about multiple medications, and report practical or other barriers to psychotherapy. Hatha yoga, with its focus on promoting good mental and physical health rather than on alleviating problems, may be a viable and attractive alternative for coping with depression. Further, hatha yoga may have additional benefits that are important, such as improved physical functioning. Hatha yoga focuses on training the body with the ultimate goal of promoting physical and emotional well- being. Yoga involves breath control (pranayama), physical postures (asanas), and meditation (dhyana). Yoga may be appealing, relatively inexpensive, and easy to access for many depressed patients. There is preliminary evidence for its efficacy as well as plausible mechanisms by which yoga might have an impact on depression. These mechanisms include: increased mindfulness, increased physical activity, decreased rumination, decreased stress reactivity (via the HPA axis), and decreased levels of inflammatory biomarkers. However, there are no well-designed, adequately controlled, and adequately powered randomized clinical trials that have evaluated the efficacy of yoga as an adjunctive or stand-alone treatment for depression. The overarching goal of this proposal is to conduct such a trial. The primary aim is to enroll 150 individuals with persisting symptoms of MDD, despite at least 8 weeks of antidepressant medication treatment, in an adequately powered randomized trial of an 8-week yoga program plus continued antidepressant treatment vs. a control group (i.e., a weekly educational program entitled Holistic Approaches to Depression, or HAD) plus continued antidepressant treatment. We aim to test whether yoga is superior to HAD in a) improving depression symptoms; b) improving work / role and family functioning; and c) improving physical functioning, pain, and physical fitness at endpoint (8 weeks) and follow-up. We hypothesize that, relative to the control group, participants in the yoga group will show more improvement in: a) the primary outcome, i.e., depressive symptoms; and b) secondary outcomes, including: psychosocial (work/ role and family) functioning, self- reported health, physical functioning, pain, and physical fitness. We will also investigate potential biological and psychological mechanisms by which yoga might have an impact on depression.